Antibody producing cells (B lymphocytes) are a heterogeneous population. I have previously identified a surface component, Lyb3, which is selectively expressed on a subclass of B cells in mice. I have shown that Lyb3 is a receptor for triggering signals from helper cells which are necessary for antibody production. During the current research year, I have been able to define a new B cell differentiation antigen, Ia.W39, which is coded for by the I-A region of the major histocompatibility complex. Ia.W39 is expressed by the same cell as Lyb3, but in contrast to Lyb3 which is a constant molecule, Ia.W39 is a private specificity of H-2b. I propose to study the structure and functional relationship between Lyb3 and Ia.W39. I will examine if the two differentiation antigens are closely associated on the B membrane by capping and mutual blocking experiments. In order to understand the functional significance of the Lyb3/Ia.W39 plus cells, I will analyze the functional profile of B cells from mutant mice which are unable to develop these mature B cells. I have already found that their frequency of mitogen reactive B cells is 100 fold reduced and I am in the process of comparing this in situ affinity maturation profile of our antibody response in defective and normal animals. The presence and significance of Ia.w39 on antigen presenting cells, i.e., macrophages, will be tested in blocking experiments. Since it is known that many cell interaction molecules map to the I-A region of the H-2 complex, and since we know that Ia.W39 is expressed on a functional subset of B cells only, it is obvious that the analysis of its functional relevance is important and will provide new insights into our understanding of B cell functions and interactions.